Mesencephalic microinjections of neurotensin-(1-13) and its C-terminal fragment, neurotensin-(8-13), potentiate brain stimulation reward.

Using the curve shift method, we assessed the effects of ventromedial mesencephalic tegmental (VMT) microinjections of an equimolar concentration of neurotensin-(1-13) (NT-(1-13)) and of its C-terminal fragment, neurotensin-(8-13) (NT-(8-13)), on operant responding for rewarding electrical stimulation of the caudal mesencephalic central gray. The effects of NT-(1-13) and NT-(8-13) on brain stimulation reward (BSR) were also compared to those of systemically administered quinpirole (0.1 and 0.2 mg/kg, s.c.), a direct dopamine agonist, and GBR-12909 (10 and 20 mg/kg, i.p.), a selective dopamine uptake blocker. At the concentration injected, NT-(8-13) was as effective as NT-(1-13) at facilitating BSR, producing significant leftward shifts of the function relating the rate of responding to the stimulation frequency (R/F function); neither form of the peptide was effective when injected in regions dorsal to the VMT. Similarly, GBR-12909 produced a parallel leftward shift of the R/F function, but, unlike NT-(1-13), also significantly increased the asymptotic rates of responding. In contrast, the high dose of quinpirole produced non-parallel leftward shifts of the R/F function and suppressed the asymptote. The similarity between the effects of neurotensin and GBR-12909 on one hand, and the differences between those of neurotensin and quinpirole on the other, suggest that activation VMT neurotensin receptors potentiate BSR by enhancing increases in dopamine neurotransmission that are contingent upon operant responding or rewarding brain stimulation, or both.(ABSTRACT TRUNCATED AT 250 WORDS)